Foxp3+ regulatory T cells maintain immune homeostasis in the skin

Cutaneous immune responses must be tightly controlled to prevent unwanted inflammation in response to innocuous antigens, while maintaining the ability to combat skin-tropic pathogens. Foxp3(+) regulatory T (T reg) cells are potent immune regulators and are found at high frequency in both human and mouse skin. Although T reg cells migrate to the skin and can dampen immune responses during experimentally induced inflammation or infection, the importance of cutaneous T reg cells for maintaining normal immune homeostasis in the skin has not been addressed. To selectively block T reg cell function in the skin, we restored the T reg cell compartment in Foxp3-deficient scurfy mice with cells whose ability to migrate to the skin was impaired because of targeted mutation of alpha-1,3-fucosyltransferase VII (Fut7). Although Fut7-deficient T reg cells were present at normal frequency and could function in all other tissues examined, these animals rapidly developed severe cutaneous inflammation. Thus, skin-resident T reg cell are essential for maintaining normal immune homeostasis at this site.